Recent studies suggest that the intracerebral norepinephrine (NE) system exerts a regulatory action on the responses of cortical metabolism and blood flow to increased functional cortical activity. We propose to investigate the role of NE in the coupling between cortical metabolic and hemodynamic changes during the spontaneous transition to REM sleep in the cat, a phenomenon known to be associated with increases in electrocortical activity and blood flow. This experimental model is unique in that it will avoid problems associated with anesthesia and non-physiologic modes of cortical activation. Our study will address the question of whether chronic NE depletion alters the REM sleep - induced changes in cortical oxidative metabolism and/or attenuates the associated blood flow responses. Adult anesthetized cats will be implanted with electrodes for polysomnography, and with bilateral cortical windows over homologous cortical areas to enable the monitoring of cortical cytochrome a,a3 and intramitochondrial NADH redox states and blood volume, by a combination of dual beam reflectance spectrophotometry and fluorometry through fiber-optic cables. The dorsal NE bundle (DB) will be unilaterally lesioned by 6-OHDA, applied through a sterotaxically placed chronic guide cannula. After recovery, the cortical EEG, EMG, eye movements, and optical parameters will be bilaterally monitored, before and after the DB lesion. The animals will serve as their own controls during the recording of the sleep state transitions. Regional cortical concentrations of NE, serotonin, dopamine, and their respective metabolites, as well as adenosine receptors, will be determined by post-mortem analysis. This project is expected to demonstrate 1) the occurrence of a REM sleep-induced increase in cortical oxidative metabolism, a phenomenon always implied but not yet directly measured; and 2) the influence of cortical NE depletion on the relationship between this metabolic change and the concomitant increase in cortical blood flow. If a dissociation between these presumably coupled phenomena is found after NE depletion, then this result may also be relevant to some of the cortical functional abnormalities present in those human neuro-degenerative diseases characterized in part by a progressive atrophy of the intracerebral NE system (e.g. Alzheimer's Disease and Parkinson's Disease).